摘要目的 采用非靶标代谢组学方法研究纳米氧化铈作用于糖尿病GK大鼠模型溃疡创面组织后所引起的相关代谢改变.方法 选用8～10周龄、体重(256±3)g雄性GK大鼠20只,按随机数字表法分为生理盐水组和纳米氧化铈组,每组10只.用皮肤取样器于大鼠背部肩胛稍后脊柱两侧对称制造2个直径8 mm的圆形深至肌层的皮肤损伤创面,创面每天给药1次,第7天处死大鼠,取材行苏木精-伊红染色法(HE)染色和代谢组学分析.利用液相色谱质谱检测大鼠创面组织中代谢产物的变化,通过主成分分析和正交偏最小二乘判别分析筛选差异代谢物.结果 HE染色结果显示,与生理盐水组相比,纳米氧化铈组大鼠皮肤创面炎症细胞较少、成纤维细胞较多且排列规则.共筛选出15个差异代谢物以及6条与实验条件相关的受到显著干扰的代谢途径,后者包括嘌呤代谢、甘氨酸、丝氨酸和苏氨酸代谢、花生四烯酸代谢、不饱和脂肪酸的生物合成、泛酸盐和辅酶A的生物合成以及柠檬酸盐循环.结论 纳米氧化铈可能通过改善GK大鼠创面的代谢网络而调节糖、脂和氨基酸代谢,且上调抗炎、抗氧化应激信号通路,从而使得创面快速愈合.

abstractsObjective To investigate the metabolic changes induced by cerium oxide (CeO2) nanoparticles in ulcerous wound tissues of diabetic GK rats using non-target metabolomics. Methods Twenty male GK rats with 8-10-week age and (256±3) g weight were randomly divided into normal saline group (10 rats) and CeO2 nanoparticles group (10 rats). Two skin lesions with a diameter of 8 mm deep to the muscle layer were created symmetrically on both sides of the spine of the dorsal scapulae of the rats. The wounds were administered with saline or CeO2 nanoparticles daily for 7 days, and the rats were sacrificed on day 7 for HE staining and metabolomics analysis. Liquid chromatography-mass spectrometry was used to detect the changes of metabolites in rat wound tissues, and differential metabolites were screened by principal component analysis and orthogonal partial least squares discriminant analysis. Results Compared with the normal saline group, the HE staining in the rats of CeO2 nanoparticles group had fewer inflammatory cells and more regular fibroblasts. A total of 15 different metabolites and 6 metabolic pathways that were significantly interfered with the experimental conditions were screened, including purine metabolism, glycine, serine and threonine metabolism, arachidonic acid metabolism, biosynthesis of unsaturated fatty acids, pantothenate and CoA biosynthesis and citrate cycle. Conclusions Nano-cerium oxide can significantly improve the wound healing by regulating glucose, lipid and amino acid metabolism of the metabolic network in GK rat wounds, and up-regulating the signaling pathways of anti-inflammatory and anti-oxidative stress.